Nutrition Containing Fat Blend

ABSTRACT

The invention relates to the use of long chain polyunsaturated fatty acids for the manufacture of a nutritional composition for feeding infants of a mother who suffered from a metabolic disorder during pregnancy and to a corresponding composition. Said composition comprises a n-3 polyunsaturated fatty acid fraction containing at least 0.1 wt docosahexaenoic acid (DHA) based on total weight of the lipid, at least 0.01 wt % n-3 docosapentaenoic acid (DPAn-3) based on total weight of the lipid, and at least 0.01 wt. % eicosapentaenoic acid (EPA) based on total weight of the lipid, wherein the sum of DHA, DPAn-3 and EPA is below 1 wt. % of total lipid.

FIELD OF THE INVENTION

The present invention relates to the use of a long chain polyunsaturatedfatty acid composition for feeding an infant of a mother who sufferedfrom a metabolic disorder during pregnancy and a nutritional compositionwith polyunsaturated fatty acids suitable for such use.

BACKGROUND OF THE INVENTION

The polyunsaturated fatty acid status of infants is of continuinginterest in the art. Several functions have been attributed to differentfatty acids. For example, docosahexaenoic acid (DHA) is the primarystructural fatty acid component in both the gray matter of the brain andthe retina of the eye and thus is essential for brain and eye function.Hence, DHA is of particular importance for the growing infant.

As a result of DHA deficiency, n-6 docosapentaenoic acid (DPA n-6) isinstead incorporated in the growing brain of the infant. This isundesirable because it is difficult to reverse and may result inimpaired neurological development. Additional, insufficient DHA may leadto a hindrance of healthy development.

DHA deficiency is of particular importance for infants of mothers whosuffered from a disease during pregnancy. Hence, particularly for theseinfants, it is of crucial importance that the infant formula provides anoptimal fatty acid profile in the infant.

DE 4 327 310 describes a milk composition from cows containingeicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3docosapentaenoic acid (DPA-n3), which is useful for promoting growth,intellectual function and sight function in children. The fatcomposition is however unsuitable for feeding to an infant because theweight ratio linoleic acid/alpha-linolenic acid (LA/ALA) is not optimal.

WO 01/78530 describes a nutritional composition containing specifiedamounts of docosahexaenoic acid (DHA) and arachidonic acid (AA) as wellas their precursor essential fatty acids ALA and LA, for providingnutrition and for enhancing neurological development of preterm infants.

WO 2004/052115 describes glyceride compositions, methods of making theglyceride compositions, and nutritional formulations containing theglyceride compositions. The glyceride compositions contain predominantlymonoglycerides and diglycerides carrying one or more long chainpolyunsaturated fatty acids. Also disclosed are methods of using theglyceride compositions and nutritional formulations

WO 98/36745 describes methods and compositions for reducing theincidence of necrotizing enterocolitis. Said compositions provide n-6and n-3 long-chain polyunsaturated fatty acids.

The object of the present invention is to provide a nutritionalcomposition with polyunsaturated fatty acids suitable for feeding aninfant of a mother who suffered from a metabolic disorder duringpregnancy.

SUMMARY OF THE INVENTION

The present inventors believe that not only DHA and AA need to beabundantly present in infant formula for optimal brain development, butalso the precursors of these fatty acids are essential because animportant part of the DHA and AA are locally synthesized in the brainsfrom its precursors. Hence, the present inventors believe that additionof DHA and/or AA alone to the standard infant formulas is insufficientto provide optimal DHA incorporation in the various neurologicaltissues. Hence the present composition also contains, besides DHA andAA, significant amounts of precursors of DHA and AA.

For an optimal de novo synthesis, the present composition contains theprecursors of DHA, including at least alpha-linolenic acid (ALA),eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (DPA-n3).However, EPA cannot be included in the composition in to high amounts,as EPA inhibits the metabolic conversion of linolenic acid (LA) to AA,another important fatty acid. The relatively low EPA amounts arecompensated for by relatively high quantities of docosapentaenoic acid(DPAn-3) in the present composition. Both precursors are essential,because they are believed to provide the precursors, which stimulate thelocal DHA synthesis.

Hence, in an optimal configuration,

the weight EPA/DHA ratio in the present composition is between 0.05 and1, which is similar or a little below the ratio of the average humanmilk;the weight ratio long chain DHA precursor [DPAn-3+EPA] per DHA ispreferably between 0.25 and 1 in order to provide sufficient DHAprecursor; andthe weight ratio DPA-n3/EPA of the present composition is between 0.25and 5. Human milk generally has a weight ratio DPA-n3/EPA above about 1.

High DPAn-3 oils, which can be suitably used, include marine oils suchas seal oil and DPAn-3-enriched fish oils. The present composition has aweight ratio DHA/DPAn-3 of between 2 and 25, slightly above the averagecontent weight ratio DHA/DPA-n3 in human milk, but a major improvementover the available infant formula containing no or only trace amounts ofDPA-n3.

In order to further improve the composition, ALA is added in significantamounts to further reduce insufficiency of DHA. The ratio ALA/DHA in thepresent composition is preferably between 5 and 25.

Furthermore, it is of great importance that arachidonic acid (AA) isincluded in the present composition, particularly in those compositionscontaining long chain precursors of docosahexaenoic acid. AA is anomega-6 fatty acid derived from linoleic acid and is found primarily infood sources such as meat, eggs and milk. AA contains twenty carbonatoms and four double bonds (20:4n-6) and is the principal omega-6 fattyacid found in the brain. Besides AA it is also of primary importancethat the lipid contains significant amounts of AA precursor, i.e. gammalinolenic acid (GLA) and linoleic acid (LA). These fatty acids providethe precursor for local synthesis of AA. Because the present compositionhas a high GLA content, i.e. preferably between 0.05 and 0.4 wt. % GLAbased on total weight of the lipid, the present composition has a lowlinoleic acid content, i.e. between 10 and 15 wt. % LA based on totalweight of the lipid.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides a nutritional composition wherein thecarbohydrate provides 40 to 75% of the total calories, the lipidprovides 20 to 50% of the total calories and the protein provides 5 to12.5% of the total calories, wherein the lipid contains at least onevegetable lipid source and a n-3 docosapentaenoic acid (DPAn-3)containing lipid source, said lipid contains an n-3 polyunsaturatedfatty acid fraction and an n-6 polyunsaturated fatty acid fraction,wherein

the n-3 polyunsaturated fatty acid fraction containsat least 0.1 wt % docosahexaenoic acid (DHA) based on total weight ofthe lipid; at least 0.01 wt % DPAn-3 based on total weight of the lipid;at least 0.01 wt. % eicosapentaenoic acid (EPA) based on total weight ofthe lipid; wherein the sum DHA, DPAn-3 and EPA is below 1 wt. % of totallipid; and between 1.9 and 3 wt. % alpha linoleic acid (ALA) based ontotal weight of the lipid; and the weight ratio: EPA/DHA ratio between0.05 and 1; (DPAn-3+EPA)/DHA 0.25 and 1; DPAn-3/EPA 0.25 and 5;DHA/DPAn-3 between 2 and 25; ALA/DHA between 5 and 25,the n-6 polyunsaturated fatty acid fraction containsbetween 0.2 and 1 wt. % arachidonic acid (AA) based on total weight ofthe lipid; and between 10 and 15 wt. % linoleic acid (LA) based on totalweight of the lipid; andthe weight ratio LA/ALA is between 5 and 10.

The present composition, which can be considered as a nutritioncontaining a lipid blend, can suitably be used for feeding healthyinfants and is particularly suitable for feeding an infant of a motherwho suffered from a metabolic disorder during pregnancy. The n-3polyunsaturated fatty acid fraction as described above providessignificant benefits for these infants. Optimally, the composition asdescribed above contains both the n-3 polyunsaturated fatty acidfraction and the n-6 polyunsaturated fatty acid fraction as describedherein.

In a further aspect the present invention provides the use of long chainpolyunsaturated fatty acids for the manufacture of a nutritionalcomposition, which is preferably a liquid composition, for feedinginfants of a mother who suffered from a metabolic disorder duringpregnancy, said composition comprising a n-3 polyunsaturated fatty acidfraction containing at least 0.1 wt % docosahexaenoic acid (DHA) basedon total weight of the lipid; and at least 0.01 wt % n-3docosapentaenoic acid (DPA-n3) based on total weight of the lipid; andat least 0.01 wt. % eicosapentaenoic acid (EPA, n3) based on totalweight of the lipid; and wherein the sum DHA, DPA-n3 and EPA is below 1wt. % of total lipid. Said nutritional composition can have any formdesired and/or suitable for feeding purposes and is preferably in theform of a liquid.

The present composition is particularly suitable for infants of motherswho suffered from one or more of diabetes type I, diabetes type II,overweight and obesity during pregnancy. These metabolic disorders are aparticular cause of reduced DHA and/or DHA precursor transmittal of themother to the infant and may result in increased DPAn-6 incorporationinto the brain membranes.

n-3 Polyunsaturated Fatty Acid Fraction:

Abbreviations for omega 3 (n-3) fatty acids:ALA=C18:3n-3=alpha-linolenic acid; EPA=20:5n-3=eicosapentaenoic acid;DPAn-3=22:5n-3=n-3 docosapentaenoic acid; DHA=22:6n-3=docosahexaenoicacid.

The present composition contains a n-3 polyunsaturated fatty acidfraction comprising at least 0.1 wt %, preferably between 0.10 and 1 wt.%, more preferably between 0.15 and 0.5 wt. % DHA based on total weightof the lipid. The present composition contains at least 0.01 wt %,preferably between 0.015 and 0.5 wt. % DPAn-3 based on total weight ofthe lipid. The EPA content is at least 0.01 wt. %, preferably between0.03 and 0.5 wt. %, even more preferably between 0.04 and 0.1 wt. %based on total weight of the lipid.

The cumulative weight % (sum) of DHA, DPA and EPA in the presentcomposition is below 1 wt. %, preferably below 0.5 wt. % of total lipid.

The present composition has a weight ratio EPA/DHA between 0.05 and 1,preferably between 0.1 and 0.5, more preferably between 0.2 and 0.5. Theweight ratio DHA/DPAn-3 of the present composition is between 2 and 25,preferably between 5 and 15. The weight ratio (DPAn-3+EPA)/DHA of thepresent composition is between 0.25 and 1. More optimally, the weightratio (precursors of DHA/DHA), i.e. (DPAn-3+EPA)/DHA, is between 0.3 and0.5. In mothers milk, the weight ratio DPAn-3/EPA is generally greaterthan 1. The present composition preferably has a weight ratio DPAn-3/EPAbetween 0.25 and 5, more preferably between 0.3 and 3. ParticularDPAn-3-enriched fish oils, selected seal oils and biotechnologicallyproduced high DPAn-3 oils may suitably be used for making thecomposition according to the present invention.

The present composition contains between 1.9 and 3 wt. %, preferablybetween 2 and 2.5 wt. % ALA based on total weight of the lipid. The wt.% ALA is slightly increased compared to mother's milk. Mothers milkgenerally contains between about 0.5 and 1.6 wt. % ALA based on totalweight of the lipid. However, mothers milk generally contains anincreased weight percentage of long chain precursors of DHA, e.g. DPAn3and EPA. Hence, the weight ratio ALA/DHA is higher in the presentcomposition compared to mother's milk, i.e. between 5 and 25 in thepresent composition, versus about 2 in mother's milk. Preferably theratio ALA/DHA in the present composition is between 7.5 and 15.

n-6 Polyunsaturated Fatty Acid Fraction:

Abbreviations for omega 6 (n-6) fatty acids: LA=18:2n-6=linoleic acid;GLA=18:3n-6=gamma-linolenic acid; DGLA=20:3n-6=dihomo-gamma-linolenicacid; AA=20:4n-6=arachidonic acid; DPAn-6=22:5n-6=n-6 docosapentaenoicacid.

The present composition contains between 0.2 and 1 wt. %, preferablybetween 0.25 and 0.75 wt. % AA based on total weight of the lipid. AAcannot be incorporated into the composition in to high amounts becauseof its pro-inflammatory effects. Hence, as a precursor of AA, thepresent composition preferably contains between 0.05 and 1 wt. %,preferably between 0.1 and 0.4 wt. %, more preferably between 0.15 and0.3 wt. % GLA based on total weight of the lipid. The high content ofGLA is included in the present composition to at least partiallycompensate for the reduced amount of DGLA in the present compositioncompared to human milk. As still the cumulative amount of precursor isrelatively low, the present composition contains a high amount of LA,i.e. between 10 and 15 wt. %, preferably between 11 and 14 wt. % LAbased on total weight of the lipid, which is slightly elevated comparedto the average content of LA in human milk, which is about 9 wt. %(Luukainen et al, Eur J Pediatr (1995) 154: 316-319). The incorporationof the present amounts of GLA and the optimal n-3 polyunsaturated fattyacid fraction does however not require excessive amounts of LA to beincluded in the present composition, i.e. above 15 wt. % LA based ontotal lipid.

The weight ratio LA/ALA in the present composition is between 5 and 10.

Infant Nutrition:

The present invention relates to nutritional formula suitable forfeeding to an infant, i.e. nutritional compositions wherein thecarbohydrate provides 40 to 75%, the lipid provides 20 to 50% and theprotein provides 5 to 12.5% of the total calories. Preferably theprotein provides 7.5 to 12.5% of the total calories.

The present composition contains at least one vegetable lipid source anda DPAn-3 containing lipid source. More preferably, the presentcomposition contains at least one lipid source selected from the groupconsisting of evening primrose oil, borage oil and blackcurrant seedoil; at least one lipid source selected from the group consisting ofcanola oil, sunflower oil, coconut oil, palm oil and soybean oil; and atleast one DPAn-3 containing lipid source. In a further preferredembodiment, the present composition also contains a fungal oil.Preferably the DPAn-3 containing lipid source contains at least 1 wt. %,even more preferably at least 2 wt. % DPA n-3 based on fatty acids ofthe DPAn-3 containing lipid source. For easy manufacturing, the DPAn-3containing lipid source contains at least 15 wt. %, more preferably atleast 20 wt. % DHA, even more preferably at least 25 wt. % DHA based onfatty acids of the DPAn-3 containing lipid source.

In a further aspect the present invention provides a method for treatinginfants of a mother who suffered from a metabolic disorder duringpregnancy by administering the present composition.

For the preparation of the present composition, a blend of animal andvegetable lipid sources is used. Because the fatty acid constitution oflipid sources can vary significantly (even if obtained from the sameplant or animal source), it is best to first analyze the lipid source tobe used and than calculate the amounts of individual oils that areneeded to achieve the present composition and admix the lipid sources.Alternatively, the skilled person can find the appropriated lipidsources in proper handbooks. The lipid source used are preferably ofnon-human origin. The fatty acids as described in the present inventionmay be provided as free fatty acids, in triglyceride form, inphospholipid form, or as a mixture of one of more of the above.

The carbohydrate of the present composition is preferably providedmainly by lactose, because it is most suitable for feeding the infant.Hence, the digestible carbohydrate fraction (carbohydrate) preferablycontains at least 50 wt. %, more preferably at least 90 wt. % lactosebased on total weight of the carbohydrate fraction.

Sleep is also of utmost importance for proper intellectual developmentof the infant. Hence, the infant preferably has reduced intestinaldiscomfort. Water-soluble indigestible fibers contribute a reducedoccurrence of intestinal discomfort such as bloating. Hence, the presentcomposition preferably also contains between 0.2 and 5 gramswater-soluble indigestible fiber per 100 kcal of the presentcomposition, more preferably between 0.5 and 1.5 gram per 100 kcal.Preferably the present composition contains at least one water-solubleindigestible fiber selected from the group consisting ofgalactooligosaccharide, fructooligosaccharide and inulin.

Optimal brain development is of particular importance for the baby thefirst few months of life. Hence, the present invention particularlyrelates to nutritional formulas, which are optimally suitable forfeeding during the first few months of life. A caloric content ofbetween 0.600 and 0.800 kcal per ml is believed to reduce intestinaldiscomfort in these young infants and thereby stimulate the uptake offatty acids. Hence, the present composition preferably contains between0.600-0.800 kcal/ml, more preferably 0.650-0.680 kcal/ml.

As the infants of mothers who suffered from a disease during pregnancymay have sometimes have to catch-up on neurological tissue development,the present invention preferably comprises nucleotides. The presentcomposition preferably also comprises between 2 and 25 mg nucleotidesand/or between 2 and 25 mg nucleosides per 100 kcal, more preferablybetween 3 and 10 mg nucleotides per 100 kcal. The present compositionpreferably contains at least 2 nucleotides selected from the groupconsisting of cytidine-5-monophosphate, uridine-5-monophosphate,adenosine-5-monophosphate, guanosine-5-monophosphate andinosine-5-monophosphate. The nucleotides and/or nucleosides furtherstimulate the immune system, acting synergistically with the otheringredients of the present composition.

EXAMPLES Example 1 Infant Formula

A liquid infant nutrition, prepared by admixing 13.9 g powder with waterto yield 100 ml final product, said liquid product comprising per 100ml:

Energy: 66 kcal

Protein: 8 en %

Digestible Carbohydrates: 44 en % (containing 7.3 g lactose)

Lipid: 48 en % (containing, based on total weight of the lipid 0.2 wt. %DHA; 0.02 wt. % DPAn-3; 0.05 wt. % EPA; 2.2 wt. % ALA, 0.2 wt. % GLA;0.35 wt. % AA, 13 wt. % LA)

Fibre: 0.8 g (containing 0.05 g fructopolysaccharide (Raftiline HP™,Orafti, Tienen, Belgium); 0.55 g transgalactooligosaccharides(Vivinal-GOS™ (Borculo Domo Ingredients, Netherlands); 0.20 g pectinhydrolysate prepared as described in EP1373543, example 1.Nucleotides: 0.89 mg Cytidine-5-monophosphate;0.55 mg Uridine-5-monophosphate;0.82 mg Adenosine-5-monophosphate;0.20 mg Guanosine-5-monophosphate;0.34 mg Inosine-5-monophosphate.Osmolarity: 300 mOsmol/l

The composition further contains choline (6 mg/100 ml) and taurine (6.3mg/100 ml); minerals and trace elements (including 2 mg zinc/100 ml) andvitamins in amounts in compliance with the international guidelines forinfant milk formula.

1. Use of long chain polyunsaturated fatty acids for the manufacture ofa liquid nutritional composition for feeding infants of a mother whosuffered from a metabolic disorder during pregnancy, said compositioncomprising a n-3 polyunsaturated fatty acid fraction containing at least0.1 wt % docosahexaenoic acid (DHA) based on total weight of the lipid,at least 0.01 wt % n-3 docosapentaenoic acid (DPAn-3) based on totalweight of the lipid, and at least 0.01 wt. % eicosapentaenoic acid (EPA)based on total weight of the lipid; wherein the sum of DHA, DPAn-3 andEPA is below 1 wt. % of total lipid.
 2. Use according to claim 1,wherein the weight ratio: EPA/DHA ratio is between 0.05 and 1;(DPAn-3+EPA)/DHA is between 0.25 and 1; DPAn-3/EPA is between 0.25 and5; and DHA/DPAn-3 is between 2 and
 25. 3. Use according to claim 1,wherein the composition further comprises n-6 polyunsaturated fatty acidfraction which contains: between 0.05 and 0.4 wt. % GLA based on totalweight of the lipid; between 0.2 and 1 wt. % arachidonic acid (AA) basedon total weight of the lipid; and between 10 and 15 wt. % linoleic acid(LA) based on total weight of the lipid.
 4. Use according to claim 1,wherein the mother suffered diabetes type I, diabetes type II, obesityor overweight during pregnancy.
 5. Nutritional composition wherein thecarbohydrate provides 40 to 75% of the total calories, the lipidprovides 20 to 50% of the total calories and the protein provides 5 to12.5% of the total calories, wherein the lipid contains at least onevegetable lipid source and a n-3 docosapentaenoic acid (DPAn-3)containing lipid source, said lipid contains a n-3 polyunsaturated fattyacid fraction and a n-6 polyunsaturated fatty acid fraction, wherein: a.the n-3 polyunsaturated fatty acid fraction contains at least 0.1 wt %docosahexaenoic acid (DHA) based on total weight of the lipid; at least0.01 wt % DPAn-3 based on total weight of the lipid; at least 0.01 wt %eicosapentaenoic acid (EPA) based on total weight of the lipid; whereinthe sum DHA, DPAn-3 and EPA is below 1 wt. % of total lipid; and between1.9 and 3 wt. % alpha linoleic acid (ALA) based on total weight of thelipid; and the weight ratio: EPA/DHA ratio between 0.05 and 1;(DPAn-3+EPA)/DHA between 0.25 and 1; DPAn-3/EPA between 0.25 and 5;DHA/DPAn-3 between 2 and 25; and ALA/DHA between 5 and 25; and b. then-6 polyunsaturated fatty acid fraction contains: between 0.2 and 1 wt.% arachidonic acid (AA) based on total weight of the lipid; and between10 and 15 wt. % linoleic acid (LA) based on total weight of the lipid;c. a weight ratio LA/ALA between 5 and
 10. 6. Composition according toclaim 5, with a caloric density between 0.65 and 0.80 kcal per ml. 7.Composition according to claim 5, comprising at least one lipid sourceselected from the group consisting of evening primrose oil, borage oiland blackcurrant seed oil; at least one lipid source selected from thegroup consisting of canola oil, sunflower oil, coconut oil, palm oil andsoybean oil; and at least one DPAn-3 containing lipid source. 8.Composition according to claim 5, comprising at least 50 wt. % lactosebased on total weight of the carbohydrate fraction.
 9. Compositionaccording to claim 5, comprising between 2 and 25 mg nucleotides and/orbetween 2 and 25 mg nucleosides per 100 kcal.
 10. Composition accordingto claim 5, comprising between 0.2 and 5 grams water-solubleindigestible fiber per 100 kcal.
 11. Composition according to claim 5comprising between 0.05 and 0.4 wt. % gamma linolenic acid (GLA) basedon total weight of the lipid.
 12. Method of treating infants of a motherwho suffered from a metabolic disorder during pregnancy by administeringa composition as described in claim
 1. 13. Use according to claim 2,wherein the composition further comprises n-6 polyunsaturated fatty acidfraction which contains: between 0.05 and 0.4 wt. % GLA based on totalweight of the lipid; between 0.2 and 1 wt. % arachidonic acid (AA) basedon total weight of the lipid; and between 10 and 15 wt. % linoleic acid(LA) based on total weight of the lipid.
 14. Use according to claim 2,wherein the mother suffered diabetes type I, diabetes type II, obesityor overweight during pregnancy.
 15. Composition according to claim 6,comprising at least one lipid source selected from the group consistingof evening primrose oil, borage oil and blackcurrant seed oil; at leastone lipid source selected from the group consisting of canola oil,sunflower oil, coconut oil, palm oil and soybean oil; and at least oneDPAn-3 containing lipid source.